Lactate treatment causes NF-kappaB activation and CD44 shedding in cultured trabecular meshwork cells.

Lactate treatment causes NF-kappaB activation and CD44 shedding in cultured trabecular meshwork cells. Research Abstract Details 

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Lactate treatment causes NF-kappaB activation and CD44 shedding in cultured trabecular meshwork cells. Abstract Text:

Adam M Miller,Michael J Nolan,John Choi,Tomoyo Koga,Xiang Shen,Beatrice Y J T Yue,Paul A Knepper,

PURPOSE: To challenge human trabecular meshwork (TM) cells using lactate to mimic cell stress and observe the effects on cell viability, NF-kappaB, and membrane type 1 matrix metalloproteinase (MT1-MMP) expression and the ectodomain shedding of soluble (s)CD44. METHODS: Human TM cells grown in 10% fetal calf serum (FCS) were incubated in 0.1% FCS with 1, 10, or 40 mM lactate or PBS for 5 and 30 minutes and 1, 3, and 6 hours. Cell viability was determined with trypan blue staining. NF-kappaB and MT1-MMP expression was evaluated through Western blot analysis of medium and the cytoplasmic and nuclear fractions. Media sCD44 concentration was determined by enzyme-linked immunosorbent assay and Western blot analysis. RESULTS: The TM cell viability was significantly decreased after incubation for 3 hours with 40 mM lactate (P < 0.01) and 6 hours with 10 and 40 mM lactate (P < 0.001). Western blot analysis showed an increased NF-kappaB p50 and MT1-MMP expression and activity by 5 minutes in lactate-treated TM cells compared with that of control cells. At 6 hours, NF-kappaB p65 was increased in nuclear fraction of lactate-treated compared with control cells. Treatment with 1 mM lactate caused an increase in the media concentration of both the 32 and 55 kDa sCD44 at 3 (P < 0.05) and 6 hours (P < 0.01). CONCLUSIONS: Lactate treatment resulted in dose- and time-dependent effects on human TM cell viability, translocation of NF-kappaB, and activation of MT1-MMP. Increased shedding of sCD44 occurred with the l mM dose of lactate. Lactate treatment of human TM cells in culture offers a useful cell model to examine the stress responses that occur in glaucoma.

Lactate treatment causes NF-kappaB activation and CD44 shedding in cultured trabecular meshwork cells. Publishing Authors By Initials

AM Miller,MJ Nolan,J Choi,T Koga,X Shen,BY Yue,PA Knepper,

For similar proteins: dna-binding proteins: nf-kappa b: transcription factor rela research abstracts see: proteins: dna-binding proteins: nf-kappa b: transcription factor rela research

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Lactate treatment causes NF-kappaB activation and CD44 shedding in cultured trabecular meshwork cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Investigative ophthalmology & visual science

VOLUME: 48

Page Numbers: 1615-21

Journal Abbreviation: Invest. Ophthalmol. Vis. Sci.

ISSN: 0146-0404

DAY: 3

MONTH: Apr

YEAR: 2007

Lactate treatment causes NF-kappaB activation and CD44 shedding in cultured trabecular meshwork cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7703701

Lactate treatment causes NF-kappaB activation and CD44 shedding in cultured trabecular meshwork cells. Keywords Mesh Terms:

KEYWORDS: Transcription Factor RelA

MESH TERMS: metabolism

Chemical & Substance for Abstract: Lactate treatment causes NF-kappaB activation and CD44 shedding in cultured trabecular meshwork cells. Information

Substance Name: Matrix Metalloproteinase 14

Registry Number: EC 3.4.24.80

Grant and Affiliation Information for Lactate treatment causes NF-kappaB activation and CD44 shedding in cultured trabecular meshwork cells.

AFFILIATION: Laboratory for Oculo-Cerebrospinal Investigation, Division of Neurosurgery, Children's Memorial Medical Center, Chicago, Illinois, USA.

Country: United States

AGENCY: United States NEI

GRANT: EY 12043

ACRONYM: EY

MEDLINETA: Invest Ophthalmol Vis Sci

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